EphA3 is a receptor tyrosine kinase that is expressed on the surface of certain solid tumors and on the vasculature of solid tumors (see, WO 2008/112192). In addition, EphA3 has been reported to be overexpressed on CD34+ cells in chronic myeloid leukemia (CML) patients in the accelerated phase and blast crisis stage (Cilloni et al., American Society of Hematology, Abstract 1092, 2008). EphA3 is also expressed on the surface of neoplastic myeloid cells, including neoplastic myeloid stem cells, in the bone marrow and peripheral blood samples obtained from patients that have chronic myeloid leukemia (CML), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), polycythemia vera (PV), essential thrombocythemia (ET), or idiopathic myelofibrosis (IM) (see, WO 2010/102244).
Angiogenesis is increased in bone marrow of AML and myelofibrosis patients (see, e.g., Padro et al., Blood 95:2637, 2000; Gianelli et al, Am. J. Clin. Path. 128:966, 2007) and high microvessel density is a poor prognostic factor in AML (e.g., Kukzu et al, Leukemia and Lymphoma 45:1185, 2004). Anti-angiogenic treatment with endostatin inhibits progression of AML in a mouse model (Schuch et al., Leukemia 19:1312, 2005). Further, new blood vessel formation is also observed in other hematological malignancies such as multiple myeloma, acute leukemias, and hematological proliferative neoplasms (see, e.g., Medinger & Mross, J. Angiogenesis Res. 2:10, 2010; and Frater et al., Diagnostic Pathol. 3:16, 2008).